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Associations of proton pump inhibitors and hospitalization due to hyponatremia: A population–based case–control study

  • Henrik Falhammar
    Correspondence
    Corresponding author at: Department of Molecular Medicine and Surgery, Karolinska Institutet, D02:04, SE-171 76 Stockholm, Sweden.
    Affiliations
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden
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  • Jonatan D. Lindh
    Affiliations
    Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
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  • Jan Calissendorff
    Affiliations
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden
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  • Jakob Skov
    Affiliations
    Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
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  • David Nathanson
    Affiliations
    Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

    Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
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  • Buster Mannheimer
    Affiliations
    Department of Clinical Science and Education at Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
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Published:August 25, 2018DOI:https://doi.org/10.1016/j.ejim.2018.08.012

      Highlights

      • Newly initiated PPIs and hospitalization due to hyponatremia was associated.
      • Lansoprazole was an exception with no association found.
      • In severe hyponatremia with newly initiated PPI, consider an alternative.
      • If the indication for PPI use remains, lansoprazole could here be an option.
      • Severe hyponatremia was not associated with ongoing PPI treatment.

      Abstract

      Background

      Small observational studies and case reports have indicated that proton pump inhibitors (PPIs) may cause hyponatremia. Whether there is a difference between the individual PPIs is yet unknown. Since PPIs are one of the most commonly prescribed groups of drugs, even a rare adverse reaction may have large implications. The objective was to study the association between PPIs and hospitalization due to hyponatremia.

      Methods

      This register–based case–control study was based on the general Swedish population. Patients hospitalized with a principal diagnosis of hyponatremia (n = 14,359) were compared to matched controls (n = 57,383). The association between newly initiated (≤90 days) and ongoing PPI use was explored using multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and socioeconomic factors.

      Results

      Adjusted ORs (95%CI) for hospitalization due to hyponatremia, compared to controls, were for newly initiated: omeprazole 2.67 (2.37–3.01); pantoprazole 2.06 (1.32–3.19); lansoprazole 1.19 (0.72–1.94); esomeprazole 2.89 (2.21–3.79) and any PPI 2.78 (2.48–3.11). Only one individual had been newly initiated on rabeprazole and had been hospitalized due to hyponatremia. Adjusted ORs (95%CI) for individuals with ongoing treatment were for: omeprazole 1.04 (0.97–1.11); pantoprazole 0.81 (0.62–1.05); lansoprazole 0.90 (0.70–1.15); rabeprazole 3.34 (0.84–11.43); esomeprazole 1.12 (0.94–1.33) and any PPI 1.04 (0.98–1.11).

      Conclusions

      With the exception of lansoprazole, this study suggests an association between any newly initiated PPI-treatment and hospitalization due to hyponatremia. Ongoing PPI use was not associated with an increased risk.

      Keywords

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